Showing papers on "Addiction published in 1996"

Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs

Abstract: THE question of whether nicotine, the neuroactive compound of tobacco, is addictive has been open to considerable scientific and public discussion. Although it can serve as a positive reinforcer in several animal species, including man, nicotine is thought to be a weak reinforcer in comparison with addictive drugs such as cocaine and heroin1,2, and has been argued to be habit forming but not addictive3,4. Here we report that intravenous nicotine in the rat, at doses known to maintain self-administration, stimulates local energy metabolism, as measured by 2-deoxyglucose autoradiography, and dopamine transmission, as estimated by brain microdialysis, in the shell of the nucleus accumbens. These neurochemical and metabolic effects are qualitatively similar to those of other drugs, such as cocaine, amphetamine and morphine, which have strong addictive properties5–7. Our results provide functional and neurochemical evidence that there are specific neurobiological commonalities between nicotine and addictive drugs.

Addictive Drugs and Brain Stimulation Reward

Abstract: Direct electrical or chemical stimulation of specific brain regions can establish response habits similar to those established by natural rewards such as food or sexual contact. Cocaine, mu and delta opiates, nicotine, phencyclidine, and cannabis each have actions that summate with rewarding electrical stimulation of the medial forebrain bundle (MFB). The reward-potentiating effects of amphetamine and opiates are associated with central sites of action where these drugs also have their direct rewarding effects, suggesting common mechanisms for drug reward per se and for drug potentiation of brain stimulation reward. The central sites at which these and perhaps other drugs of abuse potentiate brain stimulation reward and are rewarding in their own right are consistent with the hypothesis that the laboratory reward of brain stimulation and the pharmacological rewards of addictive drugs are habit forming because they act in the brain circuits that subserve more natural and biologically significant rewards.

Pathophysiological Basis of Vulnerability to Drug Abuse: Role of an Interaction Between Stress, Glucocorticoids, and Dopaminergic Neurons

Abstract: Research on drug abuse has recently focused on understanding the vulnerability to develop addiction that is present in certain individuals. These investigations suggest that addiction results from an interaction between drugs and specific individual substrates. Differences in the propensity to develop drug intake can be demonstrated in animals with equal access to drugs under stable laboratory conditions and can be predicted by drug-independent behaviors. Stress, corticosterone, and mesencephalic dopaminergic neurons seem to be organized in a pathophysiological chain determining such a vulnerability. An increased corticosterone secretion, or a higher sensitivity to the effects of this hormone, either naturally present in certain individuals or induced by stress in others, increases the vulnerability to develop drug intake, via an enhancement of the activity of mesencephalic dopaminergic neurons. These findings suggest that addiction therapies should counteract the biological peculiarity that leads some in...

Pharmacology of nicotine: addiction and therapeutics

Abstract: Nicotine maintains tobacco addiction and has therapeutic utility to aid smoking cessation and possibly to treat other medical diseases. Nicotine acts on nicotinic cholinergic receptors, which demonstrate diversity in subunit structure, function, and distribution within the nervous system, presumably mediating the complex actions of nicotine described in tobacco users. The effects of nicotine in people are influenced by the rate and route of dosing and by the development of tolerance. The metabolism of nicotine is now well characterized in humans. A few individuals with deficient C-oxidation of nicotine, unusually slow metabolism of nicotine, and little generation of cotinine have been described. Nicotine affects most organ systems in the body, although its contribution to smoking-related disease is still unclear. Nicotine as a medication is currently available as a gum, a transdermal delivery device, and a nasal spray, all of which are used for smoking cessation. Nicotine is also being investigated for therapy of ulcerative colitis, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, sleep apnea, and attention deficit disorder.

Opposite Modulation of Cocaine-Seeking Behavior by D1- and D2-Like Dopamine Receptor Agonists

Abstract: Activation of the mesolimbic dopamine system is known to trigger relapse in animal models of cocaine-seeking behavior. We found that this "priming" effect was selectively induced by D2-like, and not by D1-like, dopamine receptor agonists in rats. Moreover, D1-like receptor agonists prevented cocaine-seeking behavior induced by cocaine itself, whereas D2-like receptor agonists enhanced this behavior. These results demonstrate an important dissociation between D1- and D2-like receptor processes in cocaine-seeking behavior and support further evaluation of D1-like receptor agonists as a possible pharmacotherapy for cocaine addiction.

Addictive drugs as reinforcers: multiple partial actions on memory systems

Abstract: This review applies some new experimental findings and theoretical ideas about how reinforcers act on the neural mechanisms of learning and memory to the problem of how addictive drugs affect behaviour A basic assumption of this analysis is that all changes in behaviour, including those involved in drug addiction and the initiation of drug self-administration, require the storage of new information in the nervous system Animal studies suggest that such information is processed in several (this review deals with three) more or less independent learning and memory systems in the mammalian brain Reinforcers can interact with these systems in three ways: they activate neural substrates of observable approach or escape responses, they produce unobservable internal states that can be perceived as rewarding or aversive, and they modulate or enhance the information stored in each of the memory systems It is suggested that each addictive drug maintains its own self-administration by mimicking some subset of these actions Evidence supporting the notion of multiple memory systems and data on the actions of several drugs (amphetamine, cocaine, nicotine, alcohol and morphine) on these systems are briefly reviewed The utility of the concept of "reward" for understanding the effects of drugs on behaviour is discussed Evidence demonstrating actions of drugs on multiple neural substrates of reinforcement suggests that no single factor is likely to explain either addictive behaviour in general or self-administration in particular Some of the findings on the development and maintenance of self-administration by animals of the five exemplar drugs are discussed in the context of these ideas

Behavioural addiction: an issue for everybody?

Abstract: For many people the concept of addiction involves taking drugs Therefore it is perhaps unsurprising that most official definitions concentrate on drug ingestion Despite such definitions, there is now a growing movement which views a number of behaviours as potentially addictive, including many behaviours which do not involve the ingestion of a drug But do behavioural addictions really exist? Answers this question by examining the various commonalities (psychological, sociological and cultural) between excessive behaviours (behavioural and chemical) and by drawing on the author’s own work into fruit‐machine addiction Concludes that addictions are not just restricted to drug‐ingestion behaviours and that evidence is growing that excessive behaviours of all types do seem to have many commonalities

The biological, social and clinical bases of drug addiction: commentary and debate

Abstract: This article summarizes the main discussions at a meeting on the biological, social and clinical bases of drug addiction focused on contemporary topics in drug dependence. Four main domains are surveyed, reflecting the structure of the meeting: psychological and pharmacological factors; neurobiological substrates; risk factors (including a consideration of vulnerability from an environmental and genetic perspective); and clinical treatment. Among the topics discussed were tolerance, sensitization, withdrawal, craving and relapse; mechanisms of reinforcing actions of drugs at the behavioural, cognitive and neural levels; the role of subjective factors in drug dependence; approaches to the behavioural and molecular genetics of drug dependence; the use of functional neuroimaging; pharmaceutical and psychosocial strategies for treatment; epidemiological and sociological aspects of drug dependence. The survey takes into account the considerable disagreements and controversies arising from the discussions, but also reaches a degree of consensus in certain areas.

Evaluating the effectiveness of addiction treatments: Reasonable expectations, appropriate comparisons.

Abstract: Problems of alcohol and drug dependence are costly to society in terms of lost productivity, social disorder, and avoidable health care utilization. The dollar costs of alcohol and drug use run into billions of dollars, and from one-eighth to one-sixth of all deaths can be traced to this source. However, the efficacy of treatment for addiction is often questioned. A rationale for reasonable expectations of addiction treatments is offered, from which are derived three outcome criteria for judging the effectiveness of treatments: reduction in substance use; improvement in personal health and social function; and reduction in public health and safety risks. Based on these criteria, treatment was shown to be effective, especially when compared with alternatives like no treatment or incarceration. These evaluations, which were conducted in a scientific manner, support the continued value of public spending for carefully monitored treatment of addiction.

Efficacy of a therapeutic cocaine vaccine in rodent models

Abstract: Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing, and new therapies are urgently needed. This paper describes an immunological approach to cocaine addiction. Antibody therapy for neutralization of abused drugs has been described previously, including a recent paper demonstrating the induction of anti-cocaine antibodies. However, both the rapidity of entry of cocaine into the brain and the high doses of cocaine frequently encountered have created challenges for an antibody-based therapy. Here we demonstrate that antibodies are efficacious in an animal model of addiction. Intravenous cocaine self-administration in rats was inhibited by passive transfer of an anti-cocaine monoclonal antibody. To actively induce anti-cocaine antibodies, a cocaine vaccine was developed that generated a high-titer, long-lasting antibody response in mice. Immunized mice displayed a significant change in cocaine pharmacokinetics, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction.

Resolving the contradictions of addiction.

Abstract: Research findings on addiction are contradictory. According to biographical records and widely used diagnostic manuals, addicts use drugs compulsively, meaning that drug use is out of control and independent of its aversive consequences. This account is supported by studies that show significant heritabilities for alcoholism and other addictions and by laboratory experiments in which repeated administration of addictive drugs caused changes in neural substrates associated with reward. Epidemiological and experimental data, however, show that the consequences of drug consumption can significantly modify drug intake in addicts. The disease model can account for the compulsive features of addiction, but not occasions in which price and punishment reduced drug consumption in addicts. Conversely, learning models of addiction can account for the influence of price and punishment, but not compulsive drug taking. The occasion for this target article is that recent developments in behavioral choice theory resolve the apparent contradictions in the addiction literature. The basic argument includes the following four statements: First, repeated consumption of an addictive drug decreases its future value and the future value of competing activities. Second, the frequency of an activity is a function of its relative (not absolute) value. This implies that an activity that reduces the values of competing behaviors can increase in frequency even if its own value also declines. Third, a recent experiment (Heyman & Tanz 1995) shows that the effective reinforcement contingencies are relative to a frame of reference, and this frame of reference can change so as to favor optimal or suboptimal choice. Fourth, if the frame of reference is local, reinforcement contingencies will favor excessive drug use, but if the frame of reference is global, the reinforcement contingencies will favor controlled drug use. The transition from a global to a local frame of reference explains relapse and other compulsive features of addiction.

Understanding the means and objects of addiction: Technology, the internet, and gambling.

Abstract: This article describes how using new computer technology and the Internet for gambling can represent both the means and object of addiction. However, these technological factors do not represent the cause of addictive behavior. Given the widespread availability of computer technology and the remarkable expansion of the Internet, it is not surprising, however, that these technological advances have become associated with intemperate gambling activities. By discussing the concept of addiction and its associated social setting, neurochemistry, and gaming characteristics, this article suggests that addiction is the result of shifts in subjective experience and that new technology and the Internet can provide relatively reliable and potent contemporary vehicles for changing emotional states.

Opiates, opioids and addiction.

Abstract: Increasing our knowledge about the major addictive diseases, opiate and cocaine addiction and alcoholism, is of great importance from a public, as well as personal health perspective. Each disease is associated with profound and negative impacts on physical and mental health and also each has devastating social and economic consequences. Each of these addictive diseases has been associated with major infectious diseases including AIDS, hepatitis B, C, D and G, either through parenteral or sexual transmission. Since 1967, we have addressed the research question related to our early hypotheses on the development of an addiction, that atypical responsitivity to stress and stressors may play a central role in the acquisition and persistence of, and relapse to, drug abuse. We have been conducting studies both in humans and in animal models focused on the role of disruption of the stress responsive hypothalamic-pituitary-adrenal axis in opiate addiction, cocaine dependency and alcoholism. We also have conducted studies of the role of the endogenous opioid system in modulation of this axis, as well as the interaction of the endogenous opioid system with the dopaminergic system and other neurotransmitter and neuropeptides related to the reinforcing effects of drugs of abuse.

Internet addiction: a new disorder enters the medical lexicon

Abstract: The latest consequence of the information age may be addiction to the Internet A psychologist who has established the Centre for Online Addiction in the US says the disorder causes the same type of social problems as other established addictions Michael OReilly went on line to find physicians interested in discussing potential problems posed by the Internet

REVERSING A HISTORY OF UNMET NEEDS: Approaches to Care for Persons With Co‐occurring Addictive and Mental Disorders

Abstract: Individuals with co-occurring addictive and mental disorders are particularly vulnerable to negative outcomes. Historically, they have been treated either in mental health or addiction service settings and sometimes excluded from receiving any services at all. This article presents an overview of the prevalence and clinical correlates of co-occurring disorders, and of the historical development of separate care systems for mental and addictive disorders. The articles that follow address future treatment and service system development.

Rational Addiction to Caffeine: An Analysis of Coffee Consumption

Abstract: It is common knowledge that coffee, tea, and other beverages that contain caffeine are habit-forming. A recent medical study confirms that caffeine is strongly addictive, with subjects exhibiting "syndromes of intoxication, withdrawal, and dependence" (Strain et al. 1994, p. 1043). That study concludes that the effect is physiological, not just psychological. It is of interest to ask whether the addictive nature of "the most widely used psychoactive substance in the world" is apparent from data on consumption. There are several economic models of addiction. Among them, the rational addiction model of Becker and Murphy (1988) stands out because of its simplicity and consistency with economic theory. In this model, the utility a consumer derives from consumption depends not only on the quantity C, that is consumed, but also on the degree of addiction At. Addiction is a form of human capital (taking the form of a possibly harmful rather than beneficial stock variable); it is increased as a by-product of consumption, and it gradually depreciates as time passes. Thus current consumption affects future choices. Consuming the good now increases its desirability in the future. The Becker-Murphy model is rational and forward looking in that the consumer is aware of these future effects and weighs them in making the current consumption choice. This is in strong contrast to models that are based on assumptions of myopia and nonrational behavior. An implication of the model is that this forward-looking behavior can be detected in the data. Theory predicts that consumption data

Cocaine addiction : Hypothesis derived from imaging studies with PET : The neurobiology of cocaine addiction : From bench to bedside

Abstract: Analysis of the behavior of cocaine in the human brain with Positron Emission Tomography reveals that it is not only its affinity for the dopamine transporter that gives it its unique properties but also its fast pharmacokinetics. Its very fast uptake and clearance from the brain contrast with that of methylphenidate, another drug that inhibits the DA transporter. Methylephenidate clears from the brain at a much slower rate and is less addictive than cocaine. We postulate that periodic and frequent stimulation of the dopaminergic system secondary to chronic use of cocaine favors activation of a circuit that involves the orbitofrontal cortex, cingulate gyrus, thalamus and striatum. This circuit is abnormal in cocaine abusers and we postulate that is activation by cocaine perpetuates the compulsive administration of the drug and is perceived by the cocaine abuser as a intense desire resulting in the loss of control over the drive to take more cocaine.

Cocaine, dopamine and the endogenous opioid system.

Abstract: Cocaine addiction and opiate addiction are both major health problems in the United States today. Prospective studies from our Laboratory, which were able to detect the advent of the HIV-1 epidemic in parenteral drug abusers in New York City beginning around 1978, also showed that, from the beginning of the AIDS epidemic, cocaine abuse was a very important co-factor significantly increasing the risk for developing cocaine dependency. Fundamental studies from many laboratories including our own have shown that cocaine has profound effects on dopaminergic function, primarily from its well-established primary action of blocking the reuptake of dopamine from the synaptic cleft, an action of cocaine directed at the specific dopamine transporter. It has also been well-established by others that cocaine similarly blocks the reuptake of serotonin and norepinephrine. However, recent studies from our laboratory have shown that chronic cocaine administration profoundly disrupts the endogenous opioid system. Extensive studies have been conducted using an animal model which we have developed in our laboratory, the "binge" pattern cocaine administration model. Findings from these studies have led us to recognize the profound disruption of both dynorphin gene expression and kappa opioid receptor gene expression in a setting of chronic cocaine administration and, in turn, have led us to question a possible role of disruption of this system in the acquisition and persistence of cocaine addiction. These findings may have significance for the development of new pharmacotherapeutic agents which may be directed to specific components of the endogenous opioid system and, in particular, possibly the kappa opioid receptor system. Therefore, we have initiated studies to examine further the role of the dynorphin peptide-kappa opioid receptor system in normal physiologic function in humans.

Reinforcement processes in opiate addiction: a homeostatic model.

Abstract: The development of tolerance and dependence has traditionally been considered an integral aspect of the drug addiction process, and opiate dependence has been studied extensively as a model system in this regard. However, recent emphasis on the positive reinforcing properties of drugs has led to the suggestion that tolerance, dependence, and withdrawal may be of secondary or even negligible importance in motivating compulsive drug use. The current article argues for an integrated view of addiction in the form of a homeostatic neuroadaptation model which emphasizes the motivational significance of both the positive affective state produced by opiates and the negative affective state characteristic of drug withdrawal. The model is supported by evidence at both the behavioral and neural systems levels of analysis. Understanding the important distinction between somatic and affective components of opiate withdrawal is key to recognizing the factors which contribute to the motivational significance of opiate dependence and withdrawal. In addition, the critical role of conditioning processes in the maintenance of compulsive drug use and relapse after periods of abstention is discussed. Finally, it is argued that both the positive reinforcement produced by acute administration of a drug and the negative affective state produced by withdrawal are common to multiple classes of abused drugs, suggesting that an understanding of homeostatic neuroadaptation within motivational systems provides a key to the etiology, treatment and prevention of drug addiction.

Nicotine addiction and treatment

Abstract: The persistence of cigarette smoking despite widespread awareness of adverse health effects results from an underlying addiction to nicotine. Unaided attempts to quit smoking are generally unsuccessful. This article discusses nicotine addition and therapeutic techniques that have been or are being developed to relieve smoking withdrawal symptoms and promote abstinence from smoking. These techniques include nicotine chewing gum, skin patches, nasal sprays, and inhalers, as well as pharmacotherapies such as mecamylamine and clonidine, serotonergic treatments such as buspirone, and antidepressants such as buproprion. A nondrug approach using cigarette substitutes that mimic the airway sensations produced by cigarette smoke is also discussed.

Psychiatric Comorbidity: Prevalence in Methadone Maintenance Treatment

Abstract: This study examines prevalence rates for DSM-III-R anxiety and affective disorders in three follow-up samples of opioid addicts who were treated with methadone maintenance. At least one anxiety disorder was diagnosed in 55% of the total sample. Affective disorders were found in 58%. At least one anxiety disorder coexisted with at least one affective disorder in 36% of the sample. The research demonstrates that opiate addiction in this sample is most often associated with other comorbid psychopathology. It suggests a need for thorough assessment for general psychopathology in opioid addicts entering addiction treatment, especially assessment for anxiety and affective disorders. It also suggests the need for treatment that focuses on diagnosed mental disorders in addition to drug counseling for the substance abuse disorder.

Opioid receptors: some perspectives from early studies of their role in normal physiology, stress responsivity, and in specific addictive diseases.

Abstract: The early history of research on the possible existence of specific opioid receptors and on developing a new form of pharmacotherapy for the treatment of heroin addiction in New York City, from 1960-1973, along with the special relationships between two leading scientists conducting these research efforts, Dr. Eric Simon and Dr. Vincent P. Dole Jr., are presented in a historical perspective. The linkage of these early efforts and the subsequent identification and the elucidation of the effects of exogenous opiates acting at specific opiate receptors in human physiology, including some findings from perspective studies of heroin addicts at time of entry to and during methadone maintenance treatment, are presented in the context of the important clues which thereby were provided concerning the possible roles of the endogenous opioids in normal mammalian physiology. From many of these early clinical research findings and studies in animal models, the hypothesis that the endogenous opioids system may play an important role in stress responsivity was formulated along with the related hypothesis, first presented in the early 1970s, that an atypical responsivity to stress and stressors might be involved in the acquisition and persistence of, and relapse to specific addictive diseases, including heroin addiction, cocaine dependency and alcoholism. More recent studies of the possible involvement of the specific opioid receptors in these three addictive diseases-heroin addiction, cocaine addiction and alcoholism-from our laboratory are discussed in a historical perspective of the development of these ideas from the early research findings of not only Dr. Eric Simon, but his numerous colleagues in opioid research in the United States and throughout the world.